Anorexia contributes, to a large extent, to the cachectic state which is a significant problem in patients with cancer. Many hypotheses have been advanced to explain the inappropriately low food intake in these patients, but they have not been very conclusive. Previous work from this laboratory has suggested that derangements in central nervous system neurotransmitter metabolism, specifically involving indoleamine metabolites, may be involved in the etiology of the anorexia in cancer. These in turn appear to be secondary to disturbances in peripheral metabolism, particularly involving increased lipolysis, perhaps secondary to hyperglucagonemia, resulting in increased plasma free tryptophan making tryptophan more easily available for transport across the blood brain barrier and resulting in increased brain serotonin. The experiments to be carried out in this project involve verifying that in fact such derangements in central serotonin metabolism exists. Further experiments are directed at attempting to abolish or at least delay the onset of cancer anorexia by pharmacological means indcluding serotonin antagonists, or changing the peripheral metabolism and/or preventing penetration of tryptophan through the blood brain barrier. In preliminary studies in patients an attempt is made to verify the presence of such a mechanism in patients.